The overall goal of SIoWave, inc. is to develop a novel class of sleep-enhancing compounds that stimulate slow-wave sleep (SWS), the deepest and most restorative stage of sleep, as well as slow wave activity (SWA), a measure of sleep intensity. SWS are associated with important endocrine effects, including the release of pituitary growth hormone (GH). Loss of SWS occurs early in the course of normal aging and is nearly complete by 50 years of [unreadable] age. Simultaneous stimulation of SWS and of the associated GH release may be obtained in normal young and older adults with oral administration of gamma-hydroxybutyrate (GBH). GHB is a naturally occurring short chain metabolite of gamma-aminobutyric acid (GABA); GHB has signaling properties in the brain and high-affinity neuronal receptors. [unreadable] [unreadable] SloWave, Inc. is developing for commercialization a series of proprietary novel compounds that bind to the GHB receptor, have GHB-like effects on SWS, have a longer duration of action than GHB and/or induce SWS-associated GH release. To date, all of the preclinical activity of SloWave, Inc. has involved young rats (3-5 months of age), and these studies have demonstrated that GHB and related SloWave compounds can increase NREM (non rapid eye movement) sleep and SWA (the equivalent of SWS in humans) in rats. Since older humans represent an important market for compounds that could restore SWS, studies proposed in this Phase I application will determine if GHB and/or a GHB related compound can induce NREM sleep/SWA in an aging animal model (Specific Aim #1). In addition, because SWS is associated with GH release in humans, it is important for SIoWave, Inc. to develop an animal model that can be used to determine if any of its lead compounds are capable of inducing GH release in young and/or old animals (Specific Aim #2). In both specific aims, the effects of GHB on sleep and circulatory GH levels will be compared with the response to SIoWave's present lead compound, a GHB agonist-NCS-550, which has been shown to have pronounced effects for increasing NREM sleep/SWA in young rats. The completion of the proposed studies is expected to permit SloWave, Inc. to reach two milestones. The first milestone will be to develop an animal model that will be used in subsequent studies to determine the effects of it's patented GHB related compounds on NREM sleep and SWA in aged rats. The second milestone will be the development of an animal model for examining the effects of SIoWave lead compounds on GH release; information which can then be used in subsequent studies that would focus on the mechanisms of action by which NREM Sleep/SWA and GH are related to one another. Taken together, these results, and data collected from follow-up studies, are expected to put SIoWave, Inc. in an advantageous position for [unreadable] Commercializing compounds that have novel effects on both SWS and hormonal changes that are associated with SWS in humans. [unreadable] [unreadable]